Marine life has been the source for the discovery of compounds having varied biological activities. Some of the U.S. patents which have issued for such inventions are as follows: U.S. Pat. No. 4,548,814 for didemnins, having antiviral activity, were isolated from a marine tunicate; U.S. Pat. No. 4,729,996 discloses compounds, having antitumor properties, that were isolated from marine sponges Teichaxinella morchella and Ptilocaulis walpersi; U.S. Pat. No. 4,808,590 discloses compounds, having antiviral, antitumor and antifungal properties, isolated from the marine sponge Theonella sp.; and, U.S. Pat. No. 4,737,510 discloses compounds, having antiviral and antibacterial properties, isolated from the Caribbean sponge Agelas coniferin. Though marine life has been the source of useful chemicals, there remains a need to discover more compounds which can be used medically to treat a wide range of diseases afflicting animals and humans.
The subject invention concerns novel acetylenic alcohols isolated from the known marine sponge Cribrochalina vasculum. Several classes of noncyclic acetylenic compounds have been isolated from terrestrial plants as well as from marine organisms. Most of these compounds fall into the basic category referred to as the polyacetylenic compounds, having more than one acetylenic moieties. Several groups have reported the isolation of these polyacetylenic compounds from marine organisms. The acetylenic carbinols identified to date have been shown to contain more than one acetylenic carbinol moieties. See the following publications:
Cimino, G., A. Crispino, S. De Rosa, S. De Stefano and G. Sodano (1981) "Polyacetylenes from the sponge Petrosia ficiformis found in dark caves," Experientia 37:924-926. PA1 Fusetani, N., Y. Kato, S. Matsunaga and K. Hashimoto (1983) "Bioactive marine metabolites III. A novel polyacetylene alcohol, inhibitor of cell division in fertilized sea urchin eggs, from the marine sponge Tetrosia sp.," Tetrahedron Letters, 24 (27):2771-2774. PA1 Wright, A. E., O. J. McConnell, S. Kohmoto, M. S. Lui, W. Thompson and K. M. Snader (1987) "Duryne, a new cytotoxic agent from the marine sponge Cribrochalina dura," Tetrahedron Letters, 28 (13):1377-1380 PA1 Castiello, D., G. Cimino, S. De Rosa, B. De Stefano and G. Sodano (1980) "High molecular weight polyacetylenes from the nudibranch Peltodoris atromaculata and the sponge Petrosia ficiformis," Tetrahedron Letters 21:5047-5050 PA1 Cimino, G., A. DeGiulio, S. De Rosa, S. De Stefano and G. Sodano (1985) "Further high molecular weight polyacetylenes from the sponge Petrosia ficiformis," J. Natural Products, Vol. 48, 1:22-27 PA1 Quinoa, E. and P. Crews (1988) "Melynes, polyacetylene constituents from a Vanuatu sponge," Tetrahedron Letters, 29 (17):2037-2040 PA1 Rotem, M. and Y. Kashman (1979) "New polyacetylenes from the sponge Siphonochalina sp.," Tetrahedron Letters 34:3193-3106 PA1 Fusetani, N., M. Sugano, S. Matsunaga and K. Hashimoto (1987) "H,K-ATPase inhibitors from the marine sponge Siphonochalina truncata: Absolute configuration of siphonodiol and two related metabolites," Tetrahedron Letters, 28 (37):4311-4312 PA1 Hansen, L. and P. M. Boll (1986) "Polyacetylenes in Araliaceae: Their chemistry, biosynthesis and biological significance," Phytochemistry, 25 (2):285-293 PA1 (1) The invention compounds are non-cyclic monoacetylenic carbinols; PA1 (2) These invention compounds are the first report of branched acetylenes of this nature isolated from a natural source; PA1 (3) The invention compounds are unique in having a single terminal 3-ol, 4-en, 1-yne moiety attached to an alkyl chain; and, PA1 (4) These invention compounds are the first report of such acetylenic compounds known to possess immunosuppressive activities.
The compounds of the subject invention are clearly different from the prior art as follows: